Cell adhesion-dependent control of microRNA decay

Mammalian microRNAs (miRNAs) are highly stable in most cell types, and their decay mechanism remains largely unknown. Here we report that some miRNAs degrade rapidly upon the loss of cell adhesion. When cells are grown at low density or cells are detached by trypsinization or EGTA treatment, mature miR-141 is downregulated while miR-200c from a common primary transcript (pri-miR-200c∼141) remains unaffected. Blockade of transcription by Actinomycin D leads to rapid depletion of miR-141 with a half-life of <1 hr when cells are detached, indicating that the regulation occurs via RNA decay. A sequence motif (UGUCU) in the center of miR-141 is necessary for the regulation. We further find that many other miRNAs including miR-200a, miR-34a, miR-29b, miR-301a, and miR-21 are degraded upon cell splitting. Induced destruction of persistent regulatory molecules such as miRNAs may increase cellular plasticity and facilitate cellular remodeling in response to the changes in cell adhesion.